AB0009 DIFFERENTIALLY EXPRESSED GENES BETWEEN FLARE OF PALINDROMIC RHEUMATISM AND ACTIVE RHEUMATOID ARTHRITIS
Authors: H. H. Chen
Journal: Annals of the Rheumatic Diseases (2022)

Background Although the mechanisms of palindromic rheumatism (PR) is still unclear, an association between PR and rheumatoid arthritis (RA) has been well recognized in previous studies, with one to two-thirds of PR patients developing RA during a period of follow-up. RNA sequencing (RNA-Seq) is a next-generation sequencing (NGS) method that measures genome-wide RNA abundance. Using RNA-Seq to identify the DEGs between flare PR and active RA could help elucidate the pathogenic mechanisms of PR flare and find novel genes to predict RA progression. Objectives The aim of this study is to identify gene expression signatures between PR flare and active RA using whole blood RNA-seq. Methods We collected clinical data, and blood samples from 12 flare PR patients and 12 active RA (defined as DAS28-ESR≥3.2) patients from Taichung Veterans General hospital. We obtained high-quality RNA by using PAXGene tube for whole blood sampling and PAXGene blood RNA Kit to extract RNA. Cuffdiff (Cufflinks option) output was filtered for differentially expressed genes (DEGs) with p-value &lt; 0.05. Gene set enrichment analysis (GSEA) were performed using the GSEA version 4.0.0 with immunologic gene sets (C7 sets containing 4872 gene sets) from The Molecular Signatures Database (MSigDB). According to GSEA web suggestion, a false discovery rate (FDR) &lt; 0.25 with a p-value &lt; 0.05 was considered statistically significant. We obtained rank ordered gene list from GSEA. Results We compared flare PR and active RA using GSEA. Five of the top 12 enrichment in phenotype with flare PR was related to lipopolysaccharide (LPS), which was found in the outer membrane of Gram-negative bacteria. And other pathways were also related to immune response, e.g., B cell, T cell and macrophage. In active RA, the characteristic gene expressions were associated with immune response, such as genes up-regulated in dendritic cells, genes down-regulated in B cell, and genes up-regulated in T cells. We obtained top 3 differential gene expressions in flare PR patients and top 3 differential gene expressions in active RA patients. FCGBP, GLRX3 and RTN4R genes were significantly associated with immune response in flare PR patients. And we observed that 3 genes had statistically significant t - test result (FCGBP, p-value&lt; 0.001; GLRX3, p-value&lt; 0.001; RTN4R, p-value&lt; 0.001) (Figure 1 a, 1b and 1c ). This result showed that FCGBP, GLRX3 and RTN4R may play an important role on immune response related to flare PR. In active RA patients, 3 genes had statistically significant t - test result (HK3, p-value&lt; 0.001; HIST1H2AI, p-value= 0.002; BST1, p-value&lt;0.001) (Figure 1 d, 1e and 1f ). Figure 1. Differential gene expressions between flare PR and active RA. (a) FCGBP, (b) GLRX3, (c) RTN4R, (d) HK3, (e) HIST1H2AI, (f) BST1 Conclusion GSEA analyses showed that five of the top 12 enrichment in flare PR was related to LPS and other pathways were related to immune responses of B cell, T cell and macrophage. However, in active RA, the characteristic gene expressions included genes up-regulated in dendritic cells, genes down-regulated in B cell, and genes up-regulated in T cells, suggeting different physiological pathways from flare of PR. Disclosure of Interests None declared